Motional narrowing of the rotational spectrum of trifluoropropyne at 6550 cm(-1) by intramolecular vibrational energy redistribution

We present the basic principles of dynamic rotational spectroscopy for the highly vibrationally excited symmetric top molecule trifluoropropyne (TFP,CF3CCH). Single molecular eigenstate rotational spectra of TFP were recorded in the region of the first overtone of the nu(1) acetylenic stretching mode at 6550 cm(-1) by infrared-pulsed microwave-Fourier transform microwave triple resonance spectroscopy. The average rotational constant (B) of the highly vibrationally mixed quantum states at 6550 cm(-1) is 2909.33 MHz, a value that is 40 MHz larger than the rotational constant expected for the unperturbed C-H stretch overtone (2869.39 MHz). The average rotational constant and rotational line shape of the molecular eigenstate rotational spectra are compared to the distribution of rotational constants expected for the ensemble of normal-mode vibrational states at 6550 cm(-1) that can interact by intramolecular vibrational energy redistribution (IVR). The normal-mode population distribution at 6550 cm(-1) can be described using a Boltzmann distribution with a microcanonical temperature of 1200 K. At this energy the rotational constant distribution in the normal-mode basis set is peaked at about 2910 MHz with a width of about 230 MHz. The distribution is slightly asymmetric with a tail to the high end. The experimentally measured dynamic rotational spectra are centered at the normal-mode distribution peak; however, the spectral width is significantly narrower (40 MHz) than normal-mode ensemble width (230 MHz). This reduction of the width, along with the Lorentzian shape of the eigenstate rotational spectra when compared to the Gaussian shape of the calculated ensemble distribution, illustrates the narrowing of the spectrum due to IVR exchange. The IVR exchange rate was determined to be 120 ps, about ten times faster than the rate at which energy is redistributed from the v=2 level of the acetylenic stretch.     

A 119mSn Mossbauer study of the thermal degradation of PVC stabilised by various organotin(IV) and tin(II) compounds

^119mSn Mossbauer spectroscopy has been used to study the chemical changes undergone by a range of tin-containing stabilisers (dialkyltin dilaurates, dialkyltin bis(ethylcysteinates), stannous stearate and stannous cysteinate) during thermal degradation of PVC at 185°C. The dialkyltin-laurate and -cysteinate stabilisers are converted to the dialkyltin dichlorides. Stannous stearate and stannous cysteinate are rapidly converted into stannic oxide and stannic chloride, respectively.     

Application of the Dakin-West reaction for the synthesis of oxazole-containing dual PPARalpha/gamma agonists

An improved method for the preparation of a series of oxazole-containing dual PPARalpha/gamma agonists is described. A synthetic sequence utilizing a Dakin-West reaction was devised that allows for the introduction of the oxazole ring either late in the synthetic sequence via aminomalonate-derived chemistry or in pivotal SAR intermediates derived from aspartic acid.     

CHARMM fluctuating charge force field for proteins: II protein/solvent properties from molecular dynamics simulations using a nonadditive electrostatic model

A fluctuating charge (FQ) force field is applied to molecular dynamics simulations for six small proteins in explicit polarizable solvent represented by the TIP4P-FQ potential. The proteins include 1FSV, 1ENH, 1PGB, 1VII, 1H8K, and 1CRN, representing both helical and beta-sheet secondary structural elements. Constant pressure and temperature (NPT) molecular dynamics simulations are performed on time scales of several nanoseconds, the longest simulations yet reported using explicitly polarizable all-atom empirical potentials (for both solvent and protein) in the condensed phase. In terms of structure, the FQ force field allows deviations from native structure up to 2.5 A (with a range of 1.0 to 2.5 A). This is commensurate to the performance of the CHARMM22 nonpolarizable model and other currently existing polarizable models. Importantly, secondary structural elements maintain native structure in general to within 1 A (both helix and beta-strands), again in good agreement with the nonpolarizable case. In qualitative agreement with QM/MM ab initio dynamics on crambin (Liu et al. Proteins 2001, 44, 484), there is a sequence dependence of average condensed phase atomic charge for all proteins, a dependence one would anticipate considering the differing chemical environments around individual atoms; this is a subtle quantum mechanical feature captured in the FQ model but absent in current state-of-the-art nonpolarizable models. Furthermore, there is a mutual polarization of solvent and protein in the condensed phase. Solvent dipole moment distributions within the first and second solvation shells around the protein display a shift towards higher dipole moments (increases on the order of 0.2-0.3 Debye) relative to the bulk; protein polarization is manifested via the enhanced condensed phase charges of typical polar atoms such as backbone carbonyl oxygens, amide nitrogens, and amide hydrogens. Finally, to enlarge the sample set of proteins, gas-phase minimizations and 1 ps constant temperature simulations are performed on various-sized proteins to compare to earlier work by Kaminsky et al. (J Comp Chem 2002, 23, 1515). The present work establishes the feasibility of applying a fully polarizable force field for protein simulations and demonstrates the approach employed in extending the CHARMM force field to include these effects.     

A comparison of some friedel-crafts and grignard reactions of optically active phenyloxirane

The Friedel-Crafts reactions of optically active phenyloxirane with toluene and anisole were examined for stereospecificity. The enantiomeric ratios of the diarylethanol products were determined and compared to those of the same products obtained from the reaction of p-tolyl and p-methoxyphenyl Grignard reagents with optically active phenyloxirane. The p-tolyl Grignard and Friedel-Crafts products gave similar enantiomeric ratios (approximately 64:36 and 60:40, respectively). However, in the p-methoxyphenyl products from the Grignard and Friedel-Crafts reactions, different enantiomers predominated (ratios of 33:67 and 62:38, respectively).     

Synthesis of difunctional polystyrenes and their incorporation in block copolymers with bisphenol a polycarbonate

Block polymers of polystyrene and bisphenol A polycarbonate have been prepared and their bulk viscosities studied as functions of both shear stress and polystyrene block length. The polystyrene blocks were α,ω-diacid chlorides prepared from the reaction of “living” polystyrenes with diacid chlorides. These reactions were studied in order to discover the most effective way of preparing the polystyrene diacid chlorides. The polystyrene diacid chlorides are best prepared by reaction of disodiopolystyrene with phosgene. The flow properties of the block copolymers depend on the composition of the polymers but do not depend on the length of the polystyrene blocks.     

Determination of water soluble imidazo-1,4-benzodiazepines in blood by electron- capture gas--liquid chromatography and in urine by differential pulse polaragraphy.

A sensitive and specific electron-capture gas--liquid chromatographic (GLC--ECD) assay was developed for the determination of 8-chloro-6-(2'-fluorophenyl)-1-methyl-4H-imidazo(1,5a)(1,4)benzodiazepine (I) or 8-chloro-1,4-dimethyl-6-(2'-fluorophenyl)-4H-imidazo (1,5a)(1,4)benzodiazepine (II) in blood. The assay for both compounds involves extraction into benzene--methylene chloride (9:1) from blood buffered to pH 12.6 The overall recovery of I and II from blood is 86% +- 5.0 (S.D.) and the sensitivity limit of detection is of the order of 2 to 3 ng of I or II per milliltre of blood. The major urinary metabolite of I is 8-chloro-6-(2'-fluorophenyl)-1-hydroxymethyl-4H-imidazo(1,5a)(1,4)benzodiazepine, (IA) present as a glucuronide conjugate while 8-chloro-6-(2'-fluorophenyl)-4-hydroxyl-1-methyl-4H-imidazo(1,5a)(1,4)benzodiazepine, (IB) and 8-chloro-6-(2'-fluorophenyl)-4-hydroxy-1-hydroxymethyl-4H-imidazo(1,5a)(1,4) benzodiazepine, (IC) are minor metabolites. The major metabolite IA is extracted into benzene--methylene chloride (9:1) from urine buffered to pH 11.0 (after incubation with glucuronidase--sulfatase as pH 5.0), and analyzed by differential pulse polarography (DPP) in 0.1 M phosphate buffer PH 3). The overall recovery of IA is 84 +- 3.0% (S.D.) with a sensitivity limit of 50 ng per millilitre of urine. The metabolites of compound II have not as yet been elucidated. The GLC--ECD and DPP assays were applied to the determination of blood levels and urinary excretion in dogs following single 10 mg/kg intravenous and oral doses of I and following single 6 mg/kg intravenous and 10 mg/kg oral doses of II. Blood levels of compound I were also evaluated in man following intravenous infusion of single 10 mg doses.     

Determination of 4-amino-5-ethyl-3-thiophenecarboxylic acid methyl ester and its acid metabolite in plasma and urine by high-performance liquid chromatography

Two separate, rapid, sensitive and selective high-performance liquid chromatographic (HPLC) assays were developed for the determination of 4-amino-5-ethyl-3-thiophene-carboxylic acid methyl ester (I) and its acid metabolite, 4-amino-5-ethyl-3-thiophene-carboxylic acid (II), in plasma and urine. The analysis of I is performed directly on a hexane extract of plasma or urine (buffered to pH 11) by normal-phase HPLC analysis using a 10-micron silica gel column with an eluting solvent of hexane-ethanol (95:5) and UV detection of the effluent at 254 nm. A methyl analogue, 4-amino-5-methyl-3-thiophenecarboxylic acid methyl ester, was used as the internal standard. The analysis of II is performed on the residue of either a diethyl-ether-washed protein-free filtrate of plasma or a methylene chloride-isopropanol (95:5) extract of urine (buffered to pH 5.3) using a 10-micron alkyl phenyl (reversed-phase) column with an eluting solvent of water-methanol-1 M phosphoric acid, pH 2.5 (70:30:0.05) with UV detection of the effluent at 254 nm. An isopropyl analogue, 4-amino-5-isopropylthiophene-3-carboxylic acid (IV), was used as the internal standard. The assay of compounds I and II were applied to the determination of plasma and urine concentrations of I and II in the dog and in man following oral administration of I X HCl. The data obtained demonstrated the extremely rapid and virtually complete deesterification of I (ester) to II (acid) in both species.     

Hydrogen bonding in high-resolution protein structures: a new method to assess NMR protein geometry

An analysis of backbone hydrogen bonds has been performed on nine high-resolution protein X-ray crystal structures. Backbone hydrogen-bond geometry is compared in the context of X-ray crystal structure resolution. A strong correlation between the hydrogen-bond distance, R(HO), and the hydrogen-bond angle, theta(NHO), is observed when the X-ray crystal structure resolution is <1.00 A. Ab initio calculations were performed to substantiate these results. The angle and distance limits found in our correlation for the backbone hydrogen-bond geometry can be used to evaluate the quality of protein structures and for further NMR structure refinement.